What is this study about?

This study examines the burden, epidemiology, and outcomes of HIV-associated cryptococcal meningitis and culture-confirmed cryptococcosis in South Africa over a six-year period. Using national laboratory-based surveillance data from the GERMS-SA programme, we analyzed close to 30,000 incident cases to determine trends in incidence, demographic patterns, provincial distribution, and factors associated with in-hospital mortality. We also assessed clinical factors, including CD4 count and antifungal treatment regimens (including flucytosine use).

Why does this matter?

Cryptococcal meningitis remains one of the leading causes of death among people living with advanced HIV disease in South Africa. Although the national incidence has declined over time, the disease burden remains high, particularly among men aged 25–49 years, and in-hospital mortality remains unacceptably high at 37%. Our findings highlight critical gaps in care, which include late presentation with severe immunosuppression (CD4 <50 cells/mm³) and suboptimal access to flucytosine-containing treatment regimens.

How did this study come about?

South Africa has conducted national laboratory-based surveillance for cryptococcal disease through the GERMS-SA programme since 2005. With ongoing concerns about advanced HIV disease, the implementation of reflex cryptococcal antigen (CrAg) screening, and the registration of flucytosine in 2021, there was a need to evaluate national trends and patient outcomes in the context of these evolving public health interventions. The analysis provides a contemporary national picture to inform policy and clinical practice.

What was your role in the study?  

As the author and a member of the GERMS-SA surveillance team, I contributed to the study design, conducted data review, interpreted clinical data, and analyzed epidemiological trends.

Why should people read this article?

People should read this article because it provides a comprehensive and up-to-date national analysis of HIV-associated cryptococcal disease in a high-burden setting. For people living with HIV, it provides recommendations on the early presentation to prevent. While for clinicians, policymakers, HIV programme managers, and researchers, this study provides actionable evidence to strengthen advanced HIV disease management and reduce preventable deaths.

What impact do you hope this article will have on public health policy and healthcare access?

We hope this article reinforces national commitment to advanced HIV disease management and drives measurable improvements in access to life-saving care. Specifically, we hope the study will reinforce the importance of sustained CD4 and CrAg screening, support sustained universal access to flucytosine-containing regimens, strengthen antifungal supply chain systems, and improve retention and re-engagement in care for ART-experienced patients. Ultimately, our goal is to see fewer patients presenting with severe immunosuppression and fewer preventable deaths from cryptococcal meningitis.

Ms Liliwe Shuping is an Epidemiologist at the Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses, at the National Institute for Communicable Diseases.

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